Tobacco smoking is among the two most common preventable causes of death in the US and world- wide, and causes enormous cost to society. The continued substantial prevalence of dependent tobacco consumption and poor quit success may reflect our incomplete understanding of the nicotine dependence process. Non-pharmacological factors, such as the behavioral control exerted by internal and external drug- associated stimuli, appear to play a dominant role in nicotine dependence, more than for any other drug of abuse. Nicotine's direct effects on synaptic plasticity and associative learning may facilitate the conditioning of smoking-associated stimuli and lead to stronger, more enduring cue control over behavior. However, such theories have not been backed by direct experimental evidence in humans. of the pro- posed study is that nicotine facilitates the incidental formation o stimulus-stimulus (S-S) and stimulus- response (S-R) associations and strengthens their resistance to context-adaptive modulation. This mechanism may promote a shift towards an automatic mode of nicotine-seeking largely controlled by conditioned cues. In 3 test sessions, 34 healthy non-smokers will perform computerized tasks in which incidental S-S and S-R associations impair flexible task-adaptive performance. In the first 2 sessions, scheduled with 2 intermediate days, a nicotine (7 mg/24 hrs) or placebo patch will be administered double-blind, in a counter- balanced sequence. In each of these patch sessions, each task paradigm will employ a unique stimulus set, Hypothesis 1 allowing direct comparison of the strength of incidental associations formed in the presence of nicotine or placebo . In test session 3, scheduled one week after the second patch session, participants perform shortened versions of the tasks, once with each of the two stimulus sets, to assess the persistence of associations formed in the presence of nicotine or placebo. This will test Hypothesis 2 that the presence of nicotine during the formation of S-S and S-R associations slows their decay over time. The demonstration that nicotine promotes conditioning mechanisms in humans that could promote automatized drug-taking behavior at the expense of flexible, context-adaptive behavior would lay the groundwork for comprehensive studies aimed at demonstrating the contribution of such mechanisms to dependent tobacco consumption. A broadened, data-backed view of nicotine dependence as a disorder of drug-induced maladaptive associative learning would provide a strong scientific rationale for developing and expanding behavioral and pharmacological treatment approaches aimed at breaking over-learned stimulus-contingent behavior and promoting flexible, context-adaptive control. The present proposal constitutes the necessary first step towards substantiating theories of a specific mechanism that may mark the nicotine dependence process and explain the paradoxically high abuse potential of nicotine. Results consistent with this theoretical account would motivate studies that may lead to more effective treatments of one of the most costly disorders to society.